The overall objective of this "Research Center of Excellence in Pediatric Nephrology and Urology" is to provide a coordinated, interdisciplinary, and multi-institutional approach to study the development of the kidney during embryonic, fetal and postnatal life. The main theme of this Research Center is "Structural and Functional Development of the Kidney: Precursors of Disease in the Young and Adult." Broadly, the proposed research deals with fundamental questions of clinical relevance in Pediatric Nephrology such as the understanding of kidney morphogenesis, sodium homeostasis, and blood pressure regulation, health and disease. The experimental approaches range from examination of embryological, molecular, and cellular biological mechanisms to integrative physiological studies of renal function during development. Project 1 will investigate the regulation of renin cell identity. Project 2 will study the role of G protein - coupled receptor - kinase gene variants in the pathogenesis of hypertension. Project 3 will investigate the development of tubular polarity during normal and pathological states. Project 4 will define the intercellular signaling in obstructive uropathy. Two pilot projects will add new talent and strength to the Center. Pilot 1 deals with dopamine receptor associated proteins and hypertension. Pilot 2 addresses the role of beta-adrenergic receptor variants in genetic hypertension. The Research Center will be supported by two core facilities: administrative and education. The accomplishments during the previous funding period provide assurance that this Research Center has the necessary manpower, focus, commitment, and institutional support to accomplish the proposed goals. It is anticipated that the Center of Excellence will build on the achievements of the past five years and will lead to improved management of infants and children with renal and urological diseases.